This project addresses carcinogenesis during the perinatal period with regard both to mechanisms underlying susceptibility and to assessment of public health related phenomena. In a pharmacogenetic investigation of transplacental carcinogenesis by methylcholanthrene in mice, genetic backcrosses of C57BL/6 and DBA/2 mice were employed to produce fetuses which were, in the same mother, either inducible or noninducible for the enzymes which metabolize this carcinogen. When methylcholanthrene treatment was preceded by exposure of the mother to the noncarcinogenic enzyme inducer, beta-naphthoflavone, the numbers of tumors in both lung and liver were reduced, but only in induction-responsive fetuses. This phenomenon was observed in fetuses of both induction-responsive fetuses. This phenomenon was observed in fetuses of both induction-responsive and nonresponsive mothers, even though progeny of DBA mothers developed more tumors than did those of (C57BL/6 X DBA)F1 mothers given the same dose of methylcholanthrene. Furthermore, exposure to these agents had long-term complex effects on the responsiveness of the progeny to enzyme induction later in life. In other experiments in progress involving nitrosamines, N-nitrosodimethylamine and N-nitrosodiethylamine are being examined for their ability to cause neurogenic tumors in mice by transplacental exposure; and a tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butane (NNK), is being studied for transplacental tumorigenic potential. Both of these efforts may yield results of direct relevance to the etiology of certain childhood cancers. Another study of potential public health importance is assessing polychlorinated biphenyls as promoters and enhancers of tumors initiated by nitrosamine in the infant mouse, with examination of age at treatment, action of specific PCB congeners, and long-term biochemical changes in the tissues.